Even after an allogeneic hematopoietic stem cell transplant (HCT), outcomes in TP53-mutant (mTP53) acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) remain dismal. A first-in-class small chemical p53 reactivator is eprenetapopt (APR-246).

For a study, researchers sought to evaluate the effectiveness and safety of eprenetapopt coupled with azacitidine as maintenance treatment following HCT, they carried out a phase II, multicenter, open-label experiment. Eprenetapopt 3.7 g once daily intravenously on days 1-4 and azacitidine 36 mg/m2 once daily intravenously/subcutaneously on days 1-5 in 28-day cycles were given to patients with mTP53 MDS or AML for up to 12 cycles. Relapse-free survival (RFS) and safety were the main results.

ABut 55 of the 84 patients who were eligible for HCT were transplanted. In the end, maintenance therapy was given to 33 patients (14 AML and 19 MDS); their ages ranged from 40 to 74 years. There were 7 eprenetapopt cycles on average (range 1-12). With a median follow-up of 14.5 months, the 1-year RFS probability was 59.9% (95% CI, 41 to 74), and the median RFS was 12.5 months (95% CI, 9.6 to not estimable). With a median follow-up of 17.0 months, the 1-year OS probability was 78.8% (95% CI, 60.6 to 89.3), and the median overall survival (OS) was 20.6 months (95% CI, 14.2 to not estimable). Mortalities from the initial dosage at 30 and 60 days were 0% and 6%, respectively (n = 2). Adverse graft-versus-host disease events, both acute and chronic (all grade), were observed in 12% (n = 4) and 33% (n = 11) of patients, respectively.

Eprenetapopt and azacitidine post-HCT maintenance treatment was well tolerated in individuals with mTP53 AML and MDS. The RFS and OS results in the high-risk cohort were positive.

Reference: ascopubs.org/doi/full/10.1200/JCO.22.00181